肿瘤坏死因子抑制剂治疗自身免疫性疾病后炎症性中枢神经系统疾病的风险：系统评价和荟萃分析

肿瘤坏死因子（TNF）抑制剂已被广泛用于治疗各种自身免疫性疾病。然而，关于TNF抑制剂治疗后炎症性中枢神经系统（CNS）疾病事件的风险的持续争论，以及关于这种风险在不同自身免疫性疾病或TNF阻断药物之间如何变化的不确定性。评估抗TNF抗病性疾病的风险和抗TNF疾病的风险在抗TNF抗体中的风险或抗抗TNF的风险中的风险，以评估抗TNF的差异或抗抗TNF的风险。从成立到2024年3月1日，在PubMed，Embase和Cochrane库中进行了分离搜索。观察研究评估抗TNF疗法与炎症性中枢神经系统疾病之间相对于比较组的抗病性中枢神经系统疾病之间的关联。研究人员进行了2个研究员的独立进行研究，并进行了研究的资格评估和数据提取物。风险比（RR）用作合并分析的效果量度。主要结果是抗TNF治疗自身免疫性疾病后发生炎症性中枢神经系统事件的风险。根据不同类型的基础自身免疫性疾病和TNF抑制剂进行了次要分析。分析了1118428例自身免疫性疾病患者的十八项研究，分析了贡献超过5698532人的随访。启动TNF抑制剂后，新发炎性中枢神经系统事件的发病率在每10000人年的2.0至13.4之间。总体而言，与常规疗法相比，接触TNF抑制剂的暴露与任何炎症性CNS疾病的风险增加36％有关（RR，1.36; 95％CI，1.01-1.84; I2，49％），主要归因于脱髓延纹疾病（RR，1.38; 95％CI，1.04-1.04-1.04-12; I2; I2; I2；次级分析显示，不同类型的潜在自身免疫性疾病（风湿性疾病：RR，1.36; 95％CI，0.84-2.21;炎症性肠道疾病1.49; 95％CI，0.93-2.40; p for Suberup = .74）和TNF inf inf informant; rr = .74;抗体与Etanercept：RR，1.04； 95％CI，0.93-1.15;

Tumor necrosis factor (TNF) inhibitors have been used extensively to treat various autoimmune diseases. However, there are ongoing debates about the risk of inflammatory central nervous system (CNS) disease events following TNF inhibitor therapy, as well as uncertainty about how this risk varies across different autoimmune diseases or TNF-blocking agents.To evaluate the risk of inflammatory CNS diseases after anti-TNF initiation and assess the difference in risk among different types of underlying autoimmune diseases or TNF inhibitors.Separate searches were conducted across PubMed, Embase, and the Cochrane Library from inception until March 1, 2024.Observational studies assessing the association between anti-TNF therapy and inflammatory CNS diseases relative to a comparator group.Study eligibility assessment and data extraction were independently conducted by 2 investigators following PRISMA guidelines. The risk ratio (RR) was used as the effect measure of the pooled analysis.The primary outcome was the risk of incident inflammatory CNS events after anti-TNF therapy for autoimmune diseases. Secondary analyses were performed based on different types of underlying autoimmune diseases and TNF inhibitors.Eighteen studies involving 1 118 428 patients with autoimmune diseases contributing more than 5 698 532 person-years of follow-up were analyzed. The incidence rates of new-onset inflammatory CNS events after initiating TNF inhibitors ranged from 2.0 to 13.4 per 10 000 person-years. Overall, exposure to TNF inhibitors was associated with a 36% increased risk of any inflammatory CNS disease compared to conventional therapies (RR, 1.36; 95% CI, 1.01-1.84; I2, 49%), mainly attributed to demyelinating diseases (RR, 1.38; 95% CI, 1.04-1.81; I2, 31%). Secondary analyses revealed a similar risk of inflammatory CNS diseases across different types of underlying autoimmune diseases (rheumatic diseases: RR, 1.36; 95% CI, 0.84-2.21; inflammatory bowel disease 1.49; 95% CI, 0.93-2.40; P for subgroup = .74) and TNF inhibitors (anti-TNF monoclonal antibodies vs etanercept: RR, 1.04; 95% CI, 0.93-1.15; I2, 0%).Compared to conventional therapies, exposure to TNF inhibitors was associated with a 36% increased risk of inflammatory CNS diseases, irrespective of background autoimmune disease or TNF inhibitor type.